Rapid Response was Crucial to Containing the 1918 Flu Pandemic

BETHESDA, Md., April 2, 2007--One of the persistent riddles of the
deadly 1918 Spanish influenza pandemic is why it struck different
cities with varying severity. Why were some municipalities such as
St. Louis spared the fate of the hard-hit cities like Philadelphia
when both implemented similar public health measures? What made the
difference, according to two independent studies funded by the
National Institutes of Health (NIH), was not only how but also how
rapidly different cities responded.

Cities where public health officials imposed multiple social
containment measures within a few days after the first local cases
were recorded cut peak weekly death rates by up to half compared
with cities that waited just a few weeks to respond. Overall
mortality was also lower in cities that implemented early
interventions, but the effect was smaller. These conclusions
— the results of systematic analyses of historical data to
determine the effectiveness of public health measures in 1918
— are described in two articles published online this week in
the journal Proceedings of the National Academy of Sciences.

These important papers suggest that a primary lesson of the 1918
influenza pandemic is that it is critical to intervene early, says
Anthony S. Fauci, M.D., director of NIHs National Institute of
Allergy and Infectious Diseases (NIAID), which funded one of the
studies. While researchers are working very hard to develop
pandemic influenza vaccines and increase the speed with which they
can be made, nonpharmaceutical interventions may buy valuable time
at the beginning of a pandemic while a targeted vaccine is being
produced.

The historical analyses are part of an ongoing effort called the
Models of Infectious Disease Agent Study (MIDAS), which is
supported by NIHs National Institute of General Medical Sciences
(NIGMS). Through MIDAS, researchers have developed computer models
to examine how a future pandemic influenza virus might spread and
what interventions could minimize the impact.

Although the MIDAS models cant predict the exact spread of a
potential influenza pandemic, they have all suggested that
introducing public health measures soon after the first cases
appear could greatly reduce the number of people who get sick, says
NIGMS Director Jeremy M. Berg, Ph.D. The historical analyses help
validate the models conclusion and their potential usefulness in
preparing for a pandemic.

The ideal way to contain a potential influenza pandemic would be
to vaccinate large numbers of people before they were exposed to an
influenza virus strain that is easily transmitted from person to
person. Developing such a vaccine in advance, however, is difficult
because an influenza virus mutates as it replicates, and over time
these mutations can alter the virus enough that older vaccines are
no longer effective. With current technologies, it would take
months to develop a new vaccine after the first cases of pandemic
influenza appear.

Nonpharmaceutical interventions may limit the spread of the
virus by imposing restrictions on social gatherings where
person-to-person transmission can occur. The first of the two
historical studies, conducted by a team of researchers from NIAID,
the Department of Veterans Affairs, and the Harvard School of
Public Health, looked at 19 different public health measures that
were implemented in 17 U.S. cities in the autumn of 1918. The
second study, undertaken at Imperial College London, looked at 16
U.S. cities for which both the start and stop dates of
interventions were available.

Schools, theaters, churches and dance halls in cities across the
country were closed. Kansas City banned weddings and funerals if
more than 20 people were to be in attendance. New York mandated
staggered shifts at factories to reduce rush hour commuter traffic.
Seattles mayor ordered his constituents to wear face masks. The
first study found a clear correlation between the number of
interventions applied and the resulting peak death rate seen.
Perhaps more importantly, both studies showed that while
interventions effectively mitigated the transmission of influenza
virus in 1918, a critical factor in how much death rates were
reduced was how soon the measures were put in place.

Officials in St. Louis introduced a broad series of public
health measures to contain the flu within two days of the first
reported cases. Philadelphia, New Orleans and Boston all used
similar interventions, but they took longer to implement them, and
as a result, peak mortality rates were higher. In the most extreme
disparity, the peak mortality rate in St. Louis was only one-eighth
that of Philadelphia, the worst-hit city in the survey. In contrast
to St. Louis, Philadelphia imposed bans on public gatherings more
than two weeks after the first infections were reported. City
officials even allowed a city-wide parade to take place prior to
imposing their bans.

If St. Louis had waited another week or two, they might have
fared the same as Philadelphia, says the lead author on the first
study, Richard Hatchett, M.D., an associate director for emergency
preparedness at NIAID. Despite the fact that these cities had
dramatically different outcomes early on, all the cities in the
survey ultimately experienced significant epidemics because, in the
absence of an effective vaccine, the virus continued to spread or
recurred as cities relaxed their restrictions.

The second study also shows that the timing of when control
measures were lifted played a major part. Cities that relaxed their
restrictions after the peak of the pandemic passed often saw the
re-emergence of infection and had to reintroduce restrictions, says
Neil Ferguson, D.Phil., of Imperial College, London, the senior
author on the second study. In their paper, Dr. Ferguson and his
coauthor used mathematical models to reproduce the pattern of the
1918 pandemic in different cities. This allowed them to predict
what would have happened if cities had changed the timing of
interventions. In San Francisco, which they found to have the most
effective measures, they estimate that deaths would have been 25
percent higher had city officials not implemented their
interventions when they did. But had San Francisco left its
controls in place continuously from September 1918 through May
1919, the analysis suggests, the city might have reduced deaths by
more than 90 percent.

The fact that the early, nonpharmaceutical interventions were
effective at the height of the pandemic can inform pandemic
planners today, the authors of both studies say. In particular, the
two studies lend weight to guidance that the Centers for Disease
Control and Prevention recently released on the use of
nonpharmaceutical interventions during a pandemic (http://www.pandemicflu.gov/plan/community/mitigation.html),
which recommends precisely such a rapid early response.

NIAID is a component of the National Institutes of Health. NIAID
supports basic and applied research to prevent, diagnose and treat
infectious diseases such as HIV/AIDS and other sexually transmitted
infections, influenza, tuberculosis, malaria and illness from
potential agents of bioterrorism. NIAID also supports research on
basic immunology, transplantation and immune-related disorders,
including autoimmune diseases, asthma and allergies. News releases,
fact sheets and other NIAID-related materials are available on the
NIAID website at http://www.niaid.nih.gov.

NIGMS supports basic biomedical research that is the foundation
for advances in disease diagnosis, treatment, and prevention. For
more information about the Models of Infectious Disease Agent
Study, visit http://www.nigms.nih.gov/Initiatives/MIDAS/.

The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and Centers
and is a component of the U.S. Department of Health and Human
Services. It is the primary federal agency for conducting and
supporting basic, clinical and translational medical research, and
it investigates the causes, treatments, and cures for both common
and rare diseases. For more information about NIH and its programs,
visit www.nih.gov.

Visit PandemicFlu.gov (http://www.pandemicflu.gov/) for
one-stop access to U.S. Government information on avian and
pandemic flu.
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